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Tumor evolution of glioma intrinsic gene expression subtype associates with immunological changes in the microenvironment

By Qianghu Wang, Xin Hu, Baoli Hu, Florian Muller, Hoon Kim, Massimo Squatrito, Tom Millelsen, Lisa Scarpace, Floris Barthel, Yu-Hsi Lin, Nikunj Satani, Emmanuel Martinez-Ledesma, Edward Chang, Adriana Olar, Guocan Wang, Ana C. deCarvalho, Eskil Eskilsson, Siyuan Zheng, Amy B. Heimberger, Erik P Sulman, Do-Hyun Nam, Roel G.W. Verhaak

Posted 08 May 2016
bioRxiv DOI: 10.1101/052076 (published DOI: 10.1016/j.ccell.2017.06.003)

We leveraged IDH wild type glioblastomas and derivative neurospheres to define tumor-intrinsic transcription phenotypes. Transcriptomic multiplicity correlated with increased intratumoral heterogeneity and tumor microenvironment presence. In silico cell sorting demonstrated that M2 macrophages/microglia are the most frequent type of immune cells in the glioma microenvironment, followed by CD4 T lymphocytes and neutrophils. Hypermutation associated with CD8+ T cell enrichment. Longitudinal transcriptome analysis of 124 pairs of primary and recurrent gliomas showed expression subtype is retained in 53% of cases with no proneural to mesenchymal transition being apparent. Inference of the tumor microenvironment through gene signatures revealed a decrease in invading monocytes but a subtype dependent increase in M2 macrophages/microglia cells after disease recurrence. All expression datasets are accessible through http://recur.bioinfo.cnio.es/.

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